Estrogen-Related Receptors and Breast Cancer: A Mini Review

Abstract

The estrogen-related receptors (ERRs) ┙, ┚ and ┛ comprise the NR3B orphan subgroup within the nuclear receptor superfamily. Although the ERRs were identified based on their sequence homology to estrogen receptor alpha (ER┙), they do not bind estrogen or any other natural hormones. Recent studies have defined the roles of ERRs in the regulation of target genes at the transcriptional level as well as their participation in a broad range of physiological functions such as energy metabolism and growth progression. The expression of ERRs has been shown to be up-regulated in advanced breast cancer cells and is considered to be a negative prognostic marker for the diagnosis of the disease. This review will cover what is currently known in regards to the gene structure of ERRs in addition to their regulation, function and relationship to breast cancer. Breast cancer is a complicated disease with 200,000 women diagnosed in the United States each year. There are many factors that influence breast cancer development and progression with hormone and nuclear receptors playing critical roles. Several reviews have been written on the emerging roles of estrogen and nuclear receptors in breast cancer (reviews (Conzen 2008; Hayashi, Niwa et al. 2009; Riggins, Mazzotta et al. 2010)). In this review we will focus on the estrogen-related receptor alpha, beta and gamma (ERR┙, ┚ and ┛). ERR┙ and ERR┚ were the first orphan nuclear receptors to be cloned in the late 1980’s (Giguere, Yang et al. 1988) with ERR┛ following 10 years later (Eudy, Yao et al. 1998; Hong, Yang et al. 1999; Heard, Norby et al. 2000). Although these receptors were cloned many years ago based on their sequence homology at the DNA binding domain to estrogen receptor alpha (ER┙), their biological relevance (s) has only recently been uncovered (Giguere 2008; Villena and Kralli 2008) along with potential roles in cancer, and more specifically breast cancer.